Microscale devices for high throughput mixing and assaying of small fluid volumes have recently been developed. For example, U.S. Ser. No. 08/761,575 entitled xe2x80x9cHigh Throughput Screening Assay Systems in Microscale Fluidic Devicesxe2x80x9d by Parce et al. provides pioneering technology related to Microscale Fluidic devices, including electrokinetic devices. The devices are generally suitable for assays relating to the interaction of biological and chemical species, including enzymes and substrates, ligands and ligand binders, receptors and ligands, antibodies and antibody ligands, as well as many other assays. Because the devices provide the ability to mix fluidic reagents and assay mixing results in a single continuous process, and because minute amounts of reagents can be assayed, these microscale devices represent a fundamental advance for laboratory science.
In the electrokinetic microscale devices provided by Parce et al. above, an appropriate fluid is electrokinetically flowed into and through a microchannel microfabricated (e.g., etched, milled, laser-drilled, or otherwise fabricated) in a substrate where the channel has functional groups present on its surfaces. The groups ionize when the surface is contacted with an aqueous solution. For example, where the surface of the channel includes hydroxyl functional groups at the surface, protons can leave the surface of the channel and enter the fluid. Under such conditions, the surface possesses a net negative charge, whereas the fluid will possess an excess of protons, or positive charge, particularly localized near the interface between the channel surface and the fluid. By applying an electric field along the length of the channel, cations will flow toward the negative electrode. Movement of the positively charged species in the fluid pulls the solvent with them. The steady state velocity of this fluid movement is generally given by the equation:   v  =            ε      ⁢              xe2x80x83            ⁢      ξ      ⁢              xe2x80x83            ⁢      E              4      ⁢              xe2x80x83            ⁢      π      ⁢              xe2x80x83            ⁢      η      
where v is the solvent velocity, ∈ is the dielectric constant of the fluid, "xgr" is the zeta potential of the surface, E is the electric field strength, and xcex7 is the solvent viscosity. The solvent velocity is, therefore, directly proportional to the surface potential. Examples of particularly preferred electroosmotic fluid direction systems include, e.g., those described in International Patent Application No. WO 96/04547 to Ramsey et al., as well as U.S. Ser. No. 08/761,575 by Parce et al. Examples of additional microfluidic fluid manipulation structures relying on pumps, valves, microswitches and the like are described in, e.g., U.S. Pat. Nos. 5,271,724, 5,277,556, 5,171,132, and 5,375,979. See also, Published U.K. Patent Application No. 2 248 891 and Published European Patent Application No. 568 902.
A typical microscale device can have from a few to hundreds of fluidly connected channels chambers and/or wells. Improved methods of making microscale devices which provide for simplified manufacturing, more precise construction and the like are desirable. In addition, the ability to more easily control channel height to width ratios, thereby affecting fluid flow in the channels is also desirable. This invention provides these and many other features.
The manufacture of microfluidic devices by machining grooves, channels or the like in various substrates (glass, plastics, metals, metalloids, ceramics, polymers, organics, etc.) can be time consuming and expensive. To overcome these problems, the present invention adapts printing technologies to print channel walls, well walls, or other desired structural features on a substrate, followed by application of a material over the printed channel walls, thereby providing a laminate having an enclosed channel.
In one embodiment, the invention provides a laminate having a first surface comprising a first planar section (e.g., a sheet of glass, polymer, plastic, ceramic, metalloid, organic material, acrylic, MYLAR(copyright), or the like, having a substantially flat region) and a second surface comprising a second planar section (the second surface can be the same as the first surface in construction, or made from a different material). The first or second surface can be rigid or flexible. The laminate has a first channel disposed between the first planar section and the second planar section having at least one cross-sectional diameter between about 0.1 xcexcm and 500 xcexcm. The upper and lower walls of the channel are made from the upper and lower surfaces, with the channel having a first wall and a second wall in contact with the first planar section and the second planar section. The walls are raised in comparison to the first or second planar surfaces, e.g., as a result of having been printed on the surface, having typical heights of between about 0.1 xcexcm and 500 xcexcm, more typically between about 1 and 100 xcexcm. The walls can be constructed from adhesive materials which bond the first and second surfaces together, such as a wax, a thermoplastic, an epoxy, a pressure sensitive material, or a photo-resistive material. In typical embodiments, the walls of the channel are printed on the first and/or second surface using a printing technology such as Serigraph printing, ink jet printing, intaligo printing, offset press printing, thermal laser printing or the like. In an alternate embodiment, the surfaces are clamped together with a clamp, e.g., with the channels being printed with a non-adhesive material. Spacers are optionally used to ensure uniform distance between the sheets of material. Clamps and spacers are optionally used on applications having adhesive channel walls as well, to improve adhesion of the surfaces and to ensure uniform distance between the sheets of material. Surfaces are optionally coated to modify surface properties.
Because the upper and lower portions of the channel are made from the first and second surfaces, the channel typically has a flat top and a flat bottom. One advantage of the laminate construction of the invention over lithographic and laser ablation or other machining methods is that the portions of the channel made up of the first or second surface have the same physicochemical properties as the rest of the surface, because the channel portion is not altered by chemical or physical processes. Thus, the properties of the channels of the invention are more predictable than prior art microfluidic device construction methods. Another advantage is that the width and height of the channel walls can easily be optimized to reduce turbulence in angled portions of a channel.
An additional advantage of the present invention is that laminates with multiple sheets having fluidic structures between the sheets can easily be constructed by laminating multiple layers of materials. This increases the possible complexity of fluidic structures, increasing the applicable uses for the resulting mirofluidic devices.
Methods of forming the laminates of the invention are also provided. In the methods, first and second surfaces, each having a first planar section, are provided. A first channel having a first and a second wall is applied to the first and/or second planar section (the first and second walls are raised in comparison to the first planar surface, and have at least one cross-sectional diameter between about 0.1 xcexcm and 500 xcexcm), and the first and second planar sections are bonded. The first channel is in contact with a portion of the second planar section. The first channel is applied to the first or second planar section by printing the channel on the first or second planar section. Preferred methods of printing include Serigraph printing, ink jet printing, intaligo printing, offset press printing, and thermal laser printing.